US2003109523A1PendingUtilityA1
Bicyclic antagonists selective for the alphavbeta3 integrin
Est. expiryJul 21, 2019(expired)· nominal 20-yr term from priority
A61K 31/496A61K 31/5377C07D 215/26A61K 31/541A61K 31/537A61K 31/54C07D 215/227A61K 31/495A61K 31/4709C07D 239/14
49
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
This invention provides novel bicyclic compounds of Formula (I): wherein u, v, m, Y, G, A-B, R 1 , R 1a , R 2 , R 4 , R 5 , R 5a , and R 5b are defined in the specification which compounds exhibit activity as inhibitors of bone resorption and compounds of Formula (II) wherein u, v, m, Y, G, D, A-B, R 1 , R 1a , R 2 , R 3 R 4 , R 5 , R 5a , and R 5b are defined in the specification which compounds exhibit activity as inhibitors of bone resorption.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A compound of Formula (I):
wherein:
------ represents the presence of an optional double bond;
n is an integer of 2 to 5;
v is an integer of 0 or 1;
A-B is a diradical of the formulae:
—CH 2 —(CH 2 ) m — or
m is an integer of 1 or 2;
Y is selected from the group consisting of —O—, —CH 2 —CH 2 —, —CH═CH—,
—C≡C—, and
R 1 is hydrogen or straight chain alkyl of 1 to 6 carbon atoms; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro;
R 1a is hydrogen or straight chain alkyl of 1 to 6 carbon atoms; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 2 is hydrogen, —NHR 1 , or —OR 1 , aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from straight chain alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —S-alkyl of 1 to 6 carbon atoms, cyano, nitro, halogen and phenyl; the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro;
G is a moiety selected from the group consisting of:
u is an integer of 0 or 1;
R 4 is straight chain alkyl of 1 to 6 carbon atoms, alkoxy or phenylalkyloxy wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 5 is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms and dialkylamino of 1 to 6 carbon atoms;
R 5a is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 5b is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
provided that the optional double bond ------ is a single bond when A-B is the diradical —CH 2 —(CH 2 ) m —;
or a pharmaceutically acceptable salt thereof.
2 . A compound as defined in claim 1 wherein:
n is an integer of 2 to 4;
the moiety
is located at the a or b position of the bicyclic nucleus;
R 1 is hydrogen or straight chain alkyl of 1 to 6 carbon atoms; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or two substituents which may be the same or different and are selected from halogen, straight chain alkyl of 1 to 6 carbon atoms, and nitro; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from 2- or 3-furyl, 2- or 3-thienyl, and 2-, 3- or 4-pyridyl optionally substituted with one or two substituents which may be the same or different, and are selected from halogen, straight chain alkyl of 1 to 6 carbon atoms and nitro;
R 2 is hydrogen; aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from straight chain alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, nitro, and halogen; the heterocyclyl moiety is selected from 2- or 3-furyl, 2- or 3-thienyl, and 2-, 3- or 4-pyridyl; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from halogen, straight chain alkyl of 1 to 6 carbon atoms, and nitro; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from 2- or 3-furyl, 2- or 3-thienyl, and 2-, 3- or 4-pyridyl;
the optional double bond ----- is a single bond;
or a pharmaceutically acceptable salt thereof.
3 . A compound as defined in claim 1 wherein:
n is an integer of 2 to 4;
the moiety
is located at the a or b position of the bicyclic nucleus; A-B is the diradical —CH 2 —(CH 2 ) m —;
R 1 is hydrogen or straight chain alkyl of 1 to 6 carbon atoms; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or two substituents which may be the same or different and are selected from halogen, straight chain alkyl of 1 to 6 carbon atoms, and nitro; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from 2- or 3-furyl, 2- or 3-thienyl, and 2-, 3- or 4-pyridyl optionally substituted with one or two substituents which may be the same or different, and are selected from halogen, straight chain alkyl of 1 to 6 carbon atoms and nitro;
R 2 is hydrogen; aryl optionally substituted with one or more substituents selected from straight chain alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, nitro, and halogen; the heterocyclyl moiety is selected from 2- or 3-furyl, 2- or 3-thienyl, and 2-, 3- or 4-pyridyl; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from halogen, straight chain alkyl of 1 to 6 carbon atoms, and nitro; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from 2- or 3-furyl, 2- or 3-thienyl, and 2-, 3- or 4-pyridyl;
the optional double bond ----- is a single bond;
or a pharmaceutically acceptable salt thereof.
4 . A compound as defined in claim 1 wherein:
n is an integer of 2 to 4;
the moiety
is located at the a or b position of the bicyclic nucleus;
R 1 is H;
R 2 is H;
R 5 is H;
the optional double bond ----- is a single bond;
or a pharmaceutically acceptable salt thereof.
5 . A compound as defined in claim 1 wherein:
n is an integer of 2 to 4;
m is an integer of 1;
v is an integer of 0;
the moiety
is located at the a or b position of the bicyclic nucleus;
Y is —O—;
R 1 is H;
R 2 is H;
R 5 is H;
the optional double bond ----- is a single bond;
or a pharmaceutically acceptable salt thereof.
6 . A compound as defined in claim 1 wherein:
n is an integer of 2 to 4;
the moiety
is located at the a or b position of the bicyclic nucleus;
R 1 is H;
R 2 is H;
R 5 is H;
G is a moiety selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
7 . A compound as defined in claim 1 wherein:
n is an integer of 2 to 4;
the moiety
is located at the a or b-position of the bicyclic nucleus;
R 1 is H;
R 2 is H;
R 5 is H;
Y is —O—;
G is a moiety selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
8 . A compound as defined in claim 1 wherein:
n is an integer of 2 to 4;
the moiety
is located at the b-position of the bicyclic nucleus;
R 1 is H;
R 2 is H;
R 5 is H;
G is a moiety selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
9 . A compound as defined in claim 1 wherein:
n is an integer of 2 to 4;
the moiety
is located at the b-position of the bicyclic nucleus;
G is a moiety selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
10 . A compound as defined in claim 1 wherein:
n is an integer of 2 to 4;
A-B is the diradical —CH 2 —(CH 2 ) m —;
R 1 is H;
R 2 is H;
R 5 is H;
the moiety
is located at the a or b-position of the bicyclic nucleus;
G is a moiety selected from the group consisting of:
the optional double bond ----- is a single bond;
or a pharmaceutically acceptable salt thereof.
11 . The compound according to claim 1 4-Methyl-N-({6-[3-(1,4,5,6-tetrahydro-pyrimidin-2-ylamino)-propoxyl]1,2,3,4-tetrahydro-naphthalen-2-yl}-acetyl)-benzenesulfonamide, trifluoroacetic acid salt,or a pharmaceutically acceptable salt thereof.
12 . The compound according to claim 1 4-Methyl-N-{[7-(3-guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetyl}-benzenesulfonamide,
or a pharmaceutically acceptable salt thereof.
13 . A pharmaceutical composition useful for blocking or inhibiting bone resorption by antagonizing the (α v β 3 integrin receptor mediated binding of an osteoclast to a bone matrix which comprises administering to a mammal in need thereof an effective amount of a compound of general Formula (II);
wherein:
----- represents the presence of an optional double bond;
n is an integer of 2 to 5;
v is an integer of 0 or 1;
A-B is a diradical of the formulae:
—CH 2 —(CH 2 ) m — or
m is an integer of 1 or 2;
D is a moiety selected from the group consisting of:
—OR 3
and
Y is selected from the group consisting of —O—, —CH 2 —CH 2 —, —CH═CH—,
—C≡C—, and
R 1 is hydrogen or straight chain alkyl of 1 to 6 carbon atoms; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro;
R 1a is hydrogen or straight chain alkyl of 1 to 6 carbon atoms; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 2 is hydrogen, —NHR 1 , or —OR 1 , aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from straight chain alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —S-alkyl of 1 to 6 carbon atoms, cyano, nitro, halogen and phenyl; the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro;
R 3 is H, straight chain alkyl of 1 to 6 carbon atoms optionally substituted with a group selected from amino, hydroxyl and carboxyl or branched chain alkyl of 3 to 7 carbon atoms optionally substituted with a group selected from amino, hydroxyl and carboxyl;
G is a moiety selected from the group consisting of:
u is an integer of 0 or 1;
R 4 is straight chain alkyl of 1 to 6 carbon atoms, alkoxy or phenylalkyloxy wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 5 is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms and dialkylamino of 1 to 6 carbon atoms;
R 5a is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 5b is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
with the proviso that Y is not —O—; n is not 3 or 4; R 1 , R 2 , R 3 and R 5 are not H; D is not —OR 3 ; G is not
A-B is not
------ is not a single bond;
a)when v is 0 and substitution is at position a;
with the additional proviso that n is not 2,3 or 4; G is not
---- is not a single bond; v is not 1; A-B is not
D is not —OR 3;
a)when Y is O; R 1 , R 2 , R 3 and R 5 are H; and substitution is at position a;
with the still further proviso that when A-B is the moiety
the moiety
is located at the a,b or c positions of the bicyclic nucleus;
and with the additional proviso that the optional double bond ------ is a single bond when A-B is the diradical —CH 2 —(CH 2 ) m —;
or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier.
14 . A pharmaceutical composition according to claim 13 wherein the bone resorption disease in a mammal is selected from the group consisting of osteoporosis, hypercalcemia of malignancy, osteopenia due to bone metastases, periodontal disease, hyperparathyroidism, periarticular erosions in rheumatoid arthritis, Paget's disease, immobilization-induced osteopenia and the result of glucocorticoid treatment.
15 . A pharmaceutical composition according to claim 14 wherein the disease in a mammal characterized by bone resorption is osteoporosis.
16 . The pharmaceutical composition of claim 13 containing a compound which is selected from the group consisting of:
[6-(3-Guanidinopropoxy)-1,2,3,4-tetrahydro-napthalen-2-yl]-acetic acid ethyl ester,
[6-(3-Guanidino-propoxy)-1,2,3,4-tetrahydro-napthalen-2-yl]-acetic acid trifluoroacetate,
[7-(3-Guanidino-propoxy)-1,2,3,4-tetrahydro-napthalen-2-yl]-acetic acid trifluoroacetate,
[2-(2-Guanidino-ethoxy)-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl]-acetic acid hydrochloride,
[2-(3-Guanidino-propoxy)-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl]-acetic acid trifluoroacetate,
[2-(4-Guanidino-butoxy)-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl]-acetic acid trifluoroacetate,
[7-(4-Guanidino-butoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid trifluoroacetate,
[7-(2-Guanidino-ethoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(4-Guanidino-but-1-ynyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(5-Guanidino-pent-1-ynyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(4-Guanidino-but-1-enyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(5-Guanidino-pent-1-enyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(4-Guanidino-butyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(5-Guanidino-pentyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[1-Ethyl-7-(3-guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Trifluoroacetate
[1-Benzyl-7-(3-guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid
[1-Ethyl-7-(3-guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[1-Benzyl-7-(3-guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
[7-(4-Guanidino-butoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(2-Guanidino-ethoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid,
[7-(3-Guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(2-Guanidino-ethylcarbamoyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(3-Guanidino-propylcarbamoyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
{6-[3-(Pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid methyl ester,
{6-[3-(Pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid,
{6-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid,
{6-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid methyl ester bis(hydrochloride),
{6-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid ethyl ester, acetic acid salt,
4-Methyl-N-({6-[3-(1,4,5,6-tetrahydro-pyrimidin-2-ylamino)-propoxyl]1,2,3,4-tetrahydro-naphthalen-2-yl}-acetyl)-benzenesulfonamide, trifluoroacetic acid salt,
[6-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
[6-(4-Guanidino-butoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid trifluoroacetate,
3-[7-(2-Guanidino-ethoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-propionic acid,
3-[7-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-propionic acid,
[8-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
[8-(4-Guanidino-butoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
[1-Benzyl-7-(3-guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
3-[7-(2-Guanidino-ethoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]propionic acid nitric acid salt,
4-Methyl-N-{[7-(3-guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetyl}-benzenesulfonamide, and
[8-(5-Guanidino-pentoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid
or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier.
17 . A method of blocking or inhibiting bone resorption by antagonizing the α v β 3 integrin receptor mediated binding of an osteoclast to a bone matrix which comprises administering to a mammal in need thereof an effective amount of a compound of general Formula (II):
wherein:
------ represents the presence of an optional double bond;
n is an integer of 2 to 5;
v is an integer of 0 or 1;
A-B is a diradical of the formulae:
—CH 2 —(CH 2 ) m — or
m is an integer of 1 or 2;
D is a moiety selected from the group consisting of:
—OR 3
and
Y is selected from the group consisting of —O—, —CH 2 —CH 2 —, —CH═CH—,
—C≡C—, and
R 1 is hydrogen or straight chain alkyl of 1 to 6 carbon atoms; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro;
R 1a is hydrogen or straight chain alkyl of 1 to 6 carbon atoms; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 2 is hydrogen, —NHR 1 , or —OR 1 , aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from straight chain alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —S-alkyl of 1 to 6 carbon atoms, cyano, nitro, halogen and phenyl; the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro;
R 3 is H, straight chain alkyl of 1 to 6 carbon atoms optionally substituted with a group selected from amino, hydroxyl and carboxyl or branched chain alkyl of 3 to 7 carbon atoms optionally substituted with a group selected from amino, hydroxyl and carboxyl;
G is a moiety selected from the group consisting of:
u is an integer of 0 or 1;
R 4 is straight chain alkyl of 1 to 6 carbon atoms, alkoxy or phenylalkyloxy wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 5 is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms and dialkylamino of 1 to 6 carbon atoms;
R 5a is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 5b is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
with the proviso that Y is not —O—; n is not 3 or 4; R 1 , R 2 , R 3 and R 5 are not H; D is not —OR 3 ; G is not
---- is not a single bond;
a)when v is 0 and substitution is at position a;
with the additional proviso that n is not 2,3 or 4; G is not
---- is not a single bond; v is not 1; A-B is not
D is not —OR 3 ;
a)when Y is O; R 1 , R 2 , R 3 and R 5 are H; and substitution is at position a;
with the still further proviso that when A-B is the moiety
is located at the a,b or c positions of the bicyclic nucleus;
and with the additional proviso that the optional double bond ------ is a single bond when A-B is the diradical —CH 2 —(CH 2 ) m —;
or a pharmaceutically acceptable salt thereof.
18 . The method of claim 17 wherein the bone resorption disease in a mammal is selected from the group consisting of osteoporosis, hypercalcemia of malignancy, osteopenia due to bone metastases, periodontal disease, hyperparathyroidism, periarticular erosions in rheumatoid arthritis, Paget's disease, immobilization-induced osteopenia and the result of glucocorticoid treatment.
19 . The method of claim 18 wherein the bone resorption disease is osteoporosis.
20 . The method of claim 17 in which a compound selected from the group consisting of:
[6-(3-Guanidinopropoxy)-1,2,3,4-tetrahydro-napthalen-2-yl]-acetic acid ethyl ester,
[6-(3-Guanidino-propoxy)-1,2,3,4-tetrahydro-napthalen-2-yl]-acetic acid trifluoroacetate,
[7-(3-Guanidino-propoxy)-1,2,3,4-tetrahydro-napthalen-2-yl]-acetic acid trifluoroacetate,
[2-(2-Guanidino-ethoxy)-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl]-acetic acid hydrochloride,
[2-(3-Guanidino-propoxy)-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl]-acetic acid trifluoroacetate,
[2-(4-Guanidino-butoxy)-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl]-acetic acid trifluoroacetate,
[7-(4-Guanidino-butoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid trifluoroacetate,
[7-(2-Guanidino-ethoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[6-(4-Guanidino-butoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid trifluoroacetate,
[7-(4-Guanidino-but-1-ynyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(5-Guanidino-pent-1-ynyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(4-Guanidino-but-1-enyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(5-Guanidino-pent-1-enyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(4-Guanidino-butyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
(7-(5-Guanidino-pentyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[1-Ethyl-7-(3-guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Trifluoroacetate
[1-Benzyl-7-(3-guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid
[1-Ethyl-7-(3-guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[1-Benzyl-7-(3-guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
[7-(4-Guanidino-butoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(2-Guanidino-ethoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid,
[7-(3-Guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(2-Guanidino-ethylcarbamoyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(3-Guanidino-propylcarbamoyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
{6-[3-(Pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid methyl ester,
{6-[3-(Pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid,
{6-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid,
{6-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid methyl ester bis(hydrochloride),
{6-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid ethyl ester, acetic acid salt,
4-Methyl-N-({6-[3-(1,4,5,6-tetrahydro-pyrimidin-2-ylamino)-propoxyl]1,2,3,4-tetrahydro-naphthalen-2-yl}-acetyl)-benzenesulfonamide, trifluoroacetic acid salt,
[6-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
3-[7-(2-Guanidino-ethoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-propionic acid,
3-[7-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-propionic acid,
[8-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
[8-(4-Guanidino-butoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
[1-Benzyl-7-(3-guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
3-[7-(2-Guanidino-ethoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]propionic acid nitric acid salt,
4-Methyl-N-{[7-(3-guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetyl}-benzenesulfonamide, and
[8-(5-Guanidino-pentoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid
or a pharmaceutically acceptable salt thereof is administered.
21 . A method of treating diseases characterized by bone resorption of mineralized tissue and by bone loss, resulting from an imbalance between bone resorption and bone formation which comprises administering to a mammal in need thereof an effective amount of a compound of general Formula (II):
wherein:
------ represents the presence of an optional double bond;
n is an integer of 2 to 5;
v is an integer of 0 or 1;
A-B is a diradical of the formulae:
—CH 2 —(CH 2 ) m — or
m is an integer of 1 or 2;
D is a moiety selected from the group consisting of:
—OR 3
and
Y is selected from the group consisting of —O—, —CH 2 —CH 2 —, —CH═CH—,
—C≡C—, and
R 1 is hydrogen or straight chain alkyl of 1 to 6 carbon atoms; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro;
R 1a is hydrogen or straight chain alkyl of 1 to 6 carbon atoms; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 2 is hydrogen, —NHR 1 , or —OR 1 , aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from straight chain alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —S-alkyl of 1 to 6 carbon atoms, cyano, nitro, halogen and phenyl; the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro; phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms; heterocyclylalkyl, wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the heterocyclyl moiety is selected from a 5- or 6-membered heterocyclic ring which contains 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur optionally substituted with one or more substituents which may be the same or different, and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, cyano and nitro;
R 3 is H, straight chain alkyl of 1 to 6 carbon atoms optionally substituted with a group selected from amino, hydroxyl and carboxyl or branched chain alkyl of 3 to 7 carbon atoms optionally substituted with a group selected from amino, hydroxyl and carboxyl;
G is a moiety selected from the group consisting of:
u is an integer of 0 or 1;
R 4 is straight chain alkyl of 1 to 6 carbon atoms, alkoxy or phenylalkyloxy wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 5 is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms and dialkylamino of 1 to 6 carbon atoms;
R 5a is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
R 5b is hydrogen, straight chain alkyl of 1 to 6 carbon atoms, or phenylalkyl wherein the alkyl moiety is a straight chain alkyl of 1 to 6 carbon atoms and the phenyl moiety is optionally substituted with one or more substituents which may be the same or different and are selected from hydroxy, amino, halogen, straight chain alkyl of 1 to 6 carbon atoms, branched chain alkyl of 3 to 7 carbon atoms, cyano, nitro, alkylamino of 1 to 6 carbon atoms, and dialkylamino of 1 to 6 carbon atoms;
with the proviso that Y is not —O—; n is not 3 or 4; R 1 , R 2 , R 3 and R 5 are not H; D is not —OR 3 ; G is not
---- is not a single bond;
a)when v is 0 and substitution is at position a;
with the additional proviso that n is not 2,3 or 4; G is not
---- is not a single bond; v is not 1; A-B is not
D is not —OR 3 ;
a)when Y is 0; R 1 , R 2 , R 3 and R 5 are H; and substitution is at position a;
with the still further proviso that when A-B is the moiety
is located at the a,b or c positions of the bicyclic nucleus;
and with the additional proviso that the optional double bond ------ is a single bond when A-B is the diradical —CH 2 —(CH 2 ) m —;
or a pharmaceutically acceptable salt thereof.
22 . The method of claim 21 wherein the bone resorption of mineralized tissue and by bone loss resulting from an imbalance between bone resorption and bone formation in a mammal is selected from the group consisting of osteoporosis, hypercalcemia of malignancy, osteopenia due to bone metastases, periodontal disease, hyperparathyroidism, periarticular erosions in rheumatoid arthritis, Paget's disease, immobilization-induced osteopenia and the result of glucocorticoid treatment.
23 . The method of claim 22 wherein the disease characterized by bone loss, resulting from an imbalance between bone resorption and bone formation disease is osteoporosis.
24 . The method of claim 21 in which a compound selected from the group consisting of:
[6-(3-Guanidinopropoxy)-1,2,3,4-tetrahydro-napthalen-2-yl]-acetic acid ethyl ester,
[6-(3-Guanidino-propoxy)-1,2,3,4-tetrahydro-napthalen-2-yl]-acetic acid trifluoroacetate,
[7-(3-Guanidino-propoxy)-1,2,3,4-tetrahydro-napthalen-2-yl]-acetic acid trifluoroacetate,
[2-(2-Guanidino-ethoxy)-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl]-acetic acid hydrochloride,
[2-(3-Guanidino-propoxy)-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl]-acetic acid trifluoroacetate,
[2-(4-Guanidino-butoxy)-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl]-acetic acid trifluoroacetate,
[7-(4-Guanidino-butoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid trifluoroacetate,
[7-(2-Guanidino-ethoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[6-(4-Guanidino-butoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid trifluoroacetate,
[7-(4-Guanidino-but-1-ynyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(5-Guanidino-pent-1-ynyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(4-Guanidino-but-1-enyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(5-Guanidino-pent-1-enyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(4-Guanidino-butyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(5-Guanidino-pentyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[1-Ethyl-7-(3-guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Trifluoroacetate
[1-Benzyl-7-(3-guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid
[1-Ethyl-7-(3-guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[1-Benzyl-7-(3-guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
[7-(4-Guanidino-butoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(2-Guanidino-ethoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid,
[7-(3-Guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
[7-(2-Guanidino-ethylcarbamoyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
[7-(3-Guanidino-propylcarbamoyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid Hydrochloride,
{6-[3-(Pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid methyl ester,
{6-[3-(Pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid,
{6-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid,
{6-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid methyl ester bis(hydrochloride),
{6-[3-(1,4,5,6-Tetrahydro-pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid ethyl ester, acetic acid salt,
4-Methyl-N-({6-[3-(1,4,5,6-tetrahydro-pyrimidin-2-ylamino)-propoxyl]1,2,3,4-tetrahydro-naphthalen-2-yl}-acetyl)-benzenesulfonamide, trifluoroacetic acid salt,
[6-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
3-[7-(2-Guanidino-ethoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-propionic acid,
3-[7-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-propionic acid,
[8-(3-Guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
[8-(4-Guanidino-butoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid,
[1-Benzyl-7-(3-guanidino-propoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]-acetic acid Trifluoroacetate,
3-[7-(2-Guanidino-ethoxy)-2-oxo-1,2-dihydro-quinolin-3-yl]propionic acid nitric acid salt,
4-Methyl-N-{[7-(3-guanidino-propoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetyl}-benzenesulfonamide, and
[8-(5-Guanidino-pentoxy)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid
or a pharmaceutically acceptable salt thereof is administered.Join the waitlist — get patent alerts
Track US2003109523A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.